The focus of this program is the covalent phosphorylation of glycogen synthase from liver and its regulation by hormones such as insulin, glucagon and catecholamines. The aim would be to establish the stoichiometry of the phosphorylation of synthase, relate such phosphorylation with changes in the properties of the enzyme, and to define the number and nature of the protein kinases involved. A particular emphasis would be on cAMP-independent protein kinases and phosphorylase kinase. The possible role of Ca 2 ion and calmodulin in regulating phosphorylase kinase, or other kinases, would be addressed. These enzymological studies we would hope to correlate with experiments on isolated hepatocytes. By developing a rapid purification of glycogen synthase, initially based on raising antibodies to synthase, we would attempt to establish the relationship between the covalent phosphorylation of glycogen synthase and the actions of the hormones listed above. All evidence suggests that liver glycogen synthase is multiply phosphorylated and it is hoped to be able to link hormone action with specific site phosphorylation on glycogen synthase.